Enhanced nephrotoxicity of acetaminophen in fructose-induced hypertriglyceridemic rats: effect of partial hepatectomy.
Fructose-induced hypertriglyceridemic rats become resistant to hepatotoxicity and susceptible to nephrotoxicity of acetaminophen (APAP). Enhanced susceptibility to APAP nephrotoxicity in fructose-pretreated rats is due, at least in part, to increased renal APAP concentration at the early phase (15 and 30 min after APAP administration). However, the mechanism of an increase in renal APAP concentration is still obscure. The present study was designed to test the hypothesis that a decrease in capacity of hepatic APAP metabolism is responsible for an increase in renal APAP concentration in fructose-pretreated rats. Non-pretreated rats and fructose-pretreated rats (25% fructose in drinking water for 3 weeks) received 70% or 90% partial hepatectomy (PH) or sham operation at 1 hr before APAP administration (600 or 750 mg/kg, i.p.). PH did not potentiate APAP nephrotoxicity and renal APAP concentration, and fructose-pretreated rats showed server renal lesions and greater renal APAP concentration than non-pretreated rats irrespective of PH. The result indicates that an increase in renal APAP concentration in the fructose-pretreated rats has no relation to an alteration in hepatic metabolic capacity of APAP.
Ishida
K
K
Safety Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Tokyo, Japan.
Sakazume
M
M
Ikegami
H
H
Doi
K
K
D000082:Acetaminophen / Q000032:analysis / Q000633:toxicity*; D000818:Animals; D004357:Drug Synergism; D005632:Fructose; D006498:Hepatectomy; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology*; D007668:Kidney / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D005632:Fructose; D000082:Acetaminophen